The present invention provides a novel formulation of glyburide, N-[4-(.beta.-[2-methoxy-5-chloro-benzamido]-ethyl)-benzenesulfonyl]-N'-cyc lohexyl-urea, an anti-diabetic sulfonylurea. See The Merck Index, Tenth Edition, p. 642. The present invention further provides such formulation in a more readily manufacturable and bioavailable form than was heretofore attained. Glyburide in various formulations is available for the treatment of Type II (adult-onset) diabetes mellitus. It is effective in reducing serum glucose concentrations, effectuating control of the disease in those situaitons where non-pharmaceutical means (e.g., diet and lifestyle changes) are inadequate. See U.S. Pat. Nos. 3,426,067, 3,454,635, 3,507,961, and 3,507,954.
Subsequent to the discovery of glyburide itself, more bioavailable glyburide compositions became available as described in U.S. Pat. Nos. 3,979,520 and 4,060,634. These patents describe the use of micronized or high surface area, e.g., 3 to 10 m.sup.2 /g, glyburide in combination with various pharmaceutically acceptable excipients to obtain enhanced bioavailability. More particularly, these patents describe the use of a wetting agent in the glyburide compositions present at 5 to 10 times the weight of glyburide. The patents specifically exemplify the use of polyoxyethylene stearate as the preferred wetting agent.
In order to obtain the more bioavailable formulation as described in the above patents, the glyburide and the pharmaceutical excipients need to be granulated, following which the resulting mixture must be dried and milled before compressing into tablets. These activities require intensive use of manpower and energy in order to obtain a highly bioavailable composition.